Congenital hyperinsulinism in two siblings with ABCC8 mutation: same genotype, different phenotypes

• Main Authors: Francisco Sousa-Santos, Helder Simões, Lidia Castro-Feijóo, Paloma Cabanas Rodríguez, Ana Fernández-Marmiesse, Rebeca Saborido Fiaño, Teresa Rego, Ángel Carracedo, Jesús Barreiro Conde
• Format: Article
• Language: English
• Published: Brazilian Society of Endocrinology and Metabolism
• Series: Archives of Endocrinology and Metabolism
• Online Access: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S2359-39972018000500560&lng=en&tlng=en

SUMMARY Congenital hyperinsulinism (CHI) is a heterogenous disease caused by insulin secretion regulatory defects, being ABCC8/KCNJ11 the most commonly affected genes. Therapeutic options include diazoxide, somatostatin analogues and surgery, which is curative in focal CHI. We report the case of two siblings (born two years apart) that presented themselves with hypoketotic hyperinsulinemic persistent hypoglycemias during neonatal period. The diagnosis of diffuse CHI due to an ABCC8 compound mutation (c.3576delG and c.742C>T) was concluded. They did not benefit from diazoxide therapy (or pancreatectomy performed in patient number 1) yet responded to somatostatin analogues. Patient number 1 developed various neurological deficits (including epilepsy), however patient number 2 experienced an entirely normal neurodevelopment. We believe this case shows how previous knowledge of the firstborn sibling's disease contributed to a better and timelier medical care in patient number 2, which could potentially explain her better neurological outcome despite their same genotype.